The term "electrotransport" as used herein refers generally to the delivery of an agent (eg, a drug) through a membrane, such as skin, mucous membrane, or nails. The delivery is induced or aided by application of an electrical potential. For example, a beneficial therapeutic agent may be introduced into the systemic circulation of a human body by electrotransport delivery through the skin. A widely used electrotransport process, electromigration (also called iontophoresis), involves the electrically induced transport of charged ions. Another type of electrotransport, electroosmosis, involves the flow of a liquid, which liquid contains the agent to be delivered, under the influence of an electric field. Still another type of electrotransport process, electroporation, involves the formation of transiently-existing pores in a biological membrane by the application of an electric field. An agent can be delivered through the pores either passively (ie, without electrical assistance) or actively (ie, under the influence of an electric potential). However, in any given electrotransport process, more than one of these processes may be occurring simultaneously to a certain extent. Accordingly, the term "electrotransport", as used herein, should be given its broadest possible interpretation so that it includes the electrically induced or enhanced transport of at least one agent, which may be charged, uncharged, or a mixture thereof, whatever the specific mechanism or mechanisms by which the agent actually is transported.
Electrotransport devices use at least two electrodes that are in electrical contact with some portion of the skin, nails, mucous membrane, or other surface of the body. One electrode, commonly called the "donor" or "active" electrode, is the electrode from which the agent is delivered into the body. The other electrode, typically termed the "counter" or "return" electrode, serves to close the electrical circuit through the body. For example, if the agent to be delivered is positively charged, ie, a cation, then the anode is the active or donor electrode, while the cathode serves to complete the circuit. Alternatively, if an agent is negatively charged, ie, an anion, the cathode is the donor electrode. Additionally, both the anode and cathode may be considered donor electrodes if both anionic and cationic agent ions, or if uncharged or neutrally charged agents, are to be delivered.
Furthermore, electrotransport delivery systems generally require at least one reservoir or source of the agent to be delivered, which is typically in the form of a liquid solution or suspension. Examples of such donor reservoirs include a pouch or cavity, a porous sponge or pad, and a hydrophilic polymer or a gel matrix. Such donor reservoirs are electrically connected to, and positioned between, the anode or cathode and the body surface, to provide a fixed or renewable source of one or more agents or drugs. Electrotransport devices also have an electrical power source such as one or more batteries. Typically, one pole of the power source is electrically connected to the donor electrode, while the opposite pole is electrically connected to the counter electrode. In addition, some electrotransport devices have an electrical controller that controls the current applied through the electrodes, thereby regulating the rate of agent delivery. Furthermore, passive flux control membranes, adhesives for maintaining device contact with a body surface, insulating members, and impermeable backing members are other optional components of an electrotransport device.
All electrotransport agent delivery devices utilize an electrical circuit to electrically connect the power source (eg, a battery) and the electrodes. In very simple devices, such as those disclosed in Ariura et al U.S. Pat. No. 4,474,570, the "circuit" is merely an electrically conductive wire used to connect the battery to an electrode. Other devices use a variety of electrical components to control the amplitude, polarity, timing, waveform shape, etc. of the electric current supplied by the power source. See, for example, McNichols et al U.S. Pat. No. 5,047,007.
To date, commercial transdermal electrotransport drug delivery devices (eg, the Phoresor, sold by Iomed, Inc. of Salt Lake City, Utah; the Dupel Iontophoresis System sold by Empi, Inc. of St. Paul, Minn.; the Webster Sweat Inducer, model 3600, sold by Wescor, Inc. of Logan, Utah) have generally utilized a desk-top electrical power supply unit and a pair of skin contacting electrodes. The donor electrode contains a drug solution while the counter electrode contains a solution of a bio-compatible electrolyte salt. The "satellite" electrodes are connected to the electrical power supply unit by long (eg, 1-2 meters) electrically conductive wires or cables. Examples of desk-top electrical power supply units which use "satellite" electrode assemblies are disclosed in Jacobsen et al U.S. Pat. No. 4,141,359 (see FIGS. 3 and 4); LaPrade U.S. Pat. No. 5,006,108 (see FIG. 9); and Maurer et al U.S. Pat. No. 5,254,081 (see FIGS. 1 and 2). The power supply units in such devices have electrical controls for adjusting the amount of electrical current applied through the electrodes. The "satellite" electrodes are connected to the electrical power supply unit by long (eg, 1-2 meters) electrically conductive wires or cables. Wire connections are subject to disconnection, limit patient movement and mobility and can also be uncomfortable. The wires connecting the power supply unit to the electrodes limits their separation to the length of the wires provided. It would be an advantage to retain the benefits of a remote means for controlling the operation of an electrotransport delivery device worn by a patient (eg, in a hospital ward) without the disadvantages of intervening wires.
More recently, small self-contained electrotransport delivery devices adapted to be worn on the skin, sometimes unobtrusively under clothing, for extended periods of time have been proposed. The electrical components in such miniaturized electrotransport drug delivery devices are also preferably miniaturized, and may be either integrated circuits (ie, microchips) or small printed circuits. Electronic components, such as batteries, resistors, pulse generators, capacitors, etc., are electrically connected to form an electronic circuit that controls the amplitude, polarity, timing, waveform shape, etc. of the electric current supplied by the power source. Such small self-contained electrotransport delivery devices are disclosed for example in Tapper U.S. Pat. No. 5,224,927; Sibalis et al U.S. Pat. No. 5,224,928 and Haynes et al U.S. Pat. No. 5,246,418.
With regard to providing electrical current to electrotransport electrodes, Henley U.S. Pat. No. 5,160,316 discloses a generator driving a primary isolated current loop. The current loop feeds current to individual channels in a wide area, multi-channel electrode via a plurality of individual secondary current loops. The isolated primary current loop is disposed in adjacent, but insulated alignment with the individual secondary current loops for close inductive coupling. There is no power source for the electrotransport currents except the coupled current from the isolated primary current loop. The controls and switches for the isolated primary current loop are contained in a control box connected to the primary current loop. The current loops in Henley must be very closely coupled to have efficient transfer of current. If the current loop were physically separated by a significant distance, say several feet, from the individual current loops, the control of the electrotransport current, and hence the rate of electrotransport drug delivery, would vary considerably.
One concern, particularly with small self-contained electrotransport delivery devices that are adapted to be worn on the body and/or under clothing, is the difficulty and inconvenience of using controls or reading indicators on the device. This is also a concern (ie, from the standpoint of viewing the electrotransport delivery device or to manipulate controls thereon) when the electrotransport device is worn on an inconvenient area of the body, such as the back, the upper outer arm, and the like. Also, whereas it is convenient to have very small delivery units that are unobtrusive, it is a disadvantage if the delivery unit has controls that are too small to be effectively manipulated, or indicators (eg, LED's) that are too small to be clearly seen, by a substantial portion of the population (eg, the elderly).
It may be desired, for example, to have a start button on the electrotransport device that initiates drug delivery on demand of the patient. With a small, self-contained unit, the placement of the unit on the patient's body is usually limited to a body location that the patient can both see and reach. The limited location option may interfere with the efficacy of the therapy. Thus, in certain situations it would be an advantage to separate the controls for controlling the operation of the electrotransport delivery device from the device itself.
It may also be desired to obtain some delivery system information for the benefit of the user or a medical attendant. Examples of such delivery system information include the dosing history, amount of drug remaining in the system to be delivered, battery life, whether the system is presently in a "delivery" mode or an "off" mode, etc. There have been proposals to incorporate patient monitoring features into electrotransport drug delivery devices. One example is blood glucose monitoring for an electrotransport insulin delivery device. Thus, if the sensed glucose levels become too high, the glucose level indicator would instruct the patient to activate the device to deliver insulin. Other types of patient information besides blood glucose levels could also be sensed and displayed on an electrotransport device indicator for the benefit of the patient or a medical technician. For example, application of therapeutic drugs, whether by electrotransport or more traditional (eg, oral) dosing, can sometimes cause unwanted reactions in certain patients. These reactions can take many forms, including respiratory depression, change in head rate, change in body temperature, sweating, shaking and the like. It would be advantageous to provide this system and/or patient information to a remote indicator so that the information may be read at a remote location (eg, at a central nurse's station in a hospital ward). This would enable a nurse or attendant to take action without having to check the delivery device worn by the patient, remove the patient's clothing or otherwise disturb the patient.
It would clearly be desirable to have electrotransport delivery systems available in a configuration with the controls and indicators mounted on a control unit that is remote from the delivery unit. The present invention provides the needed improvement without diminishing the intended therapeutic efficacy of the device or the therapeutic substance to be administered.